Myotonic dystrophy type 1 (DM1), also known as Steinert's disease, is an autosomal, dominantly inherited neuromuscular disorder with a global incidence of 1 per 8000 (Harper P S: Myotonic Dystrophy 2nd ed., 1989, W.B. Saunders, London). The mutation responsible for the disease is a (CUG)n repeat expansion in the 3′ untranslated region of the DM protein kinase (DMPK) gene (Mahadevan et al., 1992. Science 255:1253-1255; Fu et al., 1992. Science 255:1256-1258; Brook et al., 1992. Cell 68:799-808). This repeat ranges in size from 5-37 repeats in the normal population to between 50-1000 repeats in adult onset cases (Harper, supra).
Adult onset DM1 is primarily characterized by myotonia, muscle wasting, and weakness, but also affects a number of organs and results in cataracts, cardiac conduction abnormalities, testicular atrophy, male baldness, and insulin resistance (Harper, supra). The main clinical symptoms of congenital myotonic dystrophy (cDM1), the most severe form of DM1, are hypotonia and neonatal respiratory distress, the latter being the major cause of mortality in cDM1 infants. Furthermore, children affected by the disease frequently suffer from mental retardation and delayed motor milestones. It has been shown that cDM1 is usually associated with extremely large CTG expansions (>1500 CTG) and evidence of delayed or arrested muscle maturation (Furling et al., 2003. Am J Pathol. 162:1001-1009; Tsilfidis et al., 1992. Nat Genet 1:192-195; Hunter et al. 1992. J Med Genet 29:774-779). Currently there is no curative therapy for this disease, and symptomatic or rehabilitation treatments are only available for the adult form of DM1.
Thus, there is a need for novel methods and products for the prognosis, diagnosis and prevention/treatment of cDM1.